The primary objective of this project is to define genetic an environmental contributions to the development and maintenance of peak bone mass in healthy, free-living subjects. Primary osteoporosis is a long term disease characterized by increased susceptibility to fractures and low bone mass at the fracture site. Its effects are felt by 20 million elderly individuals in this country, a figure that will increase as our population ages and may also be increasing due to changing lifestyles. Genetic studies are difficult because osteoporotic fractures happen so late in life. We have therefore concentrated on the study of bone mass as a risk factor for osteoporosis. Bone mass in the elderly is a function of peak bone mass and subsequent loss that starts as early as the fourth decade of life. There i a great deal of individual variation in peak bone mass and a number of family and twin studies have found that half or more of this variance is genetic. Therefore, development of peak bone mass is undoubtedly under som degree of genetic control. However, longitudinal data to estimate and characterize the influence of genetic factors on bone mass development are not available. In our study of 171 pairs of adult female twins we found evidence suggestive of the interactions of a relatively few major genes tha influence adult bone mass. There is a great deal of variation in rate of bone loss with aging, but little is known about genetic influences on this second factor contributing to osteoporosis. In the only longitudinal genetic study of bone mass loss with aging we found familial relationships in aging twins but no evidence for genetic influences. However, this study was limited to males and the radius which does not bear weight and is 90% cortical bone. We propose to continue twin studies, started up to 20 years ago, to estimat genetic and environmental influences on bone mass and extend these studies to measure genetic influences on rate of bone development and rate of loss. In addition, we will ascertain families with extreme values of bone mass in a search for evidence of segregating genes.